Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta-analysis.

Objective To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose-response meta-analysis were conducted. Methods The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels ( Results A total of 1406 participants (cohort: 466; meta-analysis: 940) were included. In the cohort study, the 0.4-0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8-1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose-response meta-analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non-linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L). Conclusion Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4-0.8 mmol/L.